crossing96/oncoscreening huggingface dataset:
[Solitary fibrous tumor of the urinary bladder: a case report].	A 41-year-old woman with an incidental tumor of the urinary bladder was referred to our hospital. Computed tomography and magnetic resonance imaging showed a tumor in the urinary bladder wall with expansive growth. Under the suspicion of leiomyoma, we performed transurethral resection of the tumor. Pathological examination of tumor specimens revealed patternless arrangements of spindle cells. Immunochemical analysis revealed tumor cells positive for CD34 and bcl-2. The final diagnosis was a solitary fibrous tumor.	bladder
Tumorigenic and prognostic significance of RASSF1A expression in low-grade (WHO grade 1 and grade 2) nonmuscle-invasive bladder cancer.	OBJECTIVE: To investigate RASSF1A expression in an attempt to understand the effect of RASSF1A in low-grade, nonmuscle-invasive bladder cancer (NMIBC). METHODS: A total of 101 tumor tissues and normal donor-matched adjacent tissues from patients with primary low-grade NMIBC were selected. RASSF1A expression was measured by quantitative real-time polymerase chain reaction and is expressed as the ratio between the normal tissue level and the tumor tissue level (N/T ratio). RASSF1A promoter methylation was assessed using methylation-specific polymerase chain reaction. RESULTS: RASSF1A mRNA expression was significantly lower in patients with RASSF1A methylation than in those with no methylation (P = .046), and RASSF1A mRNA expression was lower in the tumor tissues than in the matched normal bladder mucosa (P < .001). The RASSF1A N/T ratio was greater in grade 2 and large tumors than in grade 1 and small tumors (P < .05 for each). Kaplan-Meier estimates revealed that the differences in the RASSF1A N/T ratio were associated with significant differences in the interval to tumor recurrence (P = .018) in low-grade NMIBC. Multivariate Cox regression analysis showed that the RASSF1A N/T ratio (hazards ratio 2.354, P = .015) was an independent predictor of recurrence. CONCLUSION: Decreased RASSF1A expression correlates with the transition from normal mucosa to bladder cancer and has prognostic value in low-grade NMIBC.	bladder
Low molecular weight cyclin E is associated with p27-resistant, high-grade, high-stage and invasive bladder cancer.	Expression of low molecular weight (LMW) isoforms of cyclin E is a strong predictor of poor outcome in patients with breast cancer. The purpose of this study was to examine the expression of full-length and LMW cyclin E in bladder cancer cell lines and patient tumors. We used western blotting, immunoprecipitation and kinase assays to examine the expression and activity of key cell cycle-regulatory proteins in various human bladder cell lines, both tumorigenic and non-tumorigenic. We also analyzed cyclin E expression, kinase activity and immune complex binding partners in 43 tissue samples from grade 2 and 3 transitional cell carcinomas. Cyclin E was overexpressed and LMW isoforms were present only in bladder cancer cells. Overexpression of LMW isoforms of cyclin E and increased cyclin E kinase activity were both significantly associated with tumorigenicity of the bladder cell lines (p = 0.005 and 0.022, respectively). Binding of the cyclin-dependent kinase inhibitors p21 and p27 to LMW cyclin E did not inhibit the kinase activity of cyclin E and cyclin-dependent kinase 2 in primary tumor samples overexpressing LMW cyclin E. Full-length and LMW cyclin E were significantly overexpressed in grade 3 tumors compared with grade 2 tumors (p = 0.004). Finally, LMW cyclin E levels were significantly associated with a non-papillary growth pattern (p = 0.031) and invasiveness (p = 0.021) of the bladder tumors and poor overall survival (p = 0.06). These results suggest that LMW cyclin E can be used as a new prognostic marker for bladder cancer.	bladder
PIK3CA mutation spectrum in urothelial carcinoma reflects cell context-dependent signaling and phenotypic outputs.	Although activating mutations of PIK3CA are frequent in urothelial carcinoma (UC), no information is available on their specific effects in urothelial cells or the basis for the observed mutation spectrum, which has a large excess of helical domain mutations. We investigated the phenotypic and signaling consequences of hotspot and UC-specific rare PIK3CA mutations in immortalized normal human urothelial cells (NHUC) and mouse fibroblasts (NIH3T3). Our results indicate that in NHUC, rare mutant forms and all three hotspot mutant forms of PIK3CA can activate the PI3K/AKT pathway. The relative frequency at which helical domain and kinase domain mutations are found in UC is related to their potency in inducing signaling downstream of AKT and to the phenotypic effects induced in this cell type (E545K>E542K>H1047R). Helical domain mutations E542K and E545K conferred a significant proliferative advantage at confluence and under conditions of nutrient depletion, and increased cellular resistance to anoikis. Both helical and kinase domain mutants induced increased NHUC cell motility and migration towards a chemoattractant, though no significant differences were found between the mutant forms. In NIH3T3 cells, the kinase domain mutant H1047R induced high levels of AKT activation, but helical domain mutants were significantly less potent and this was reflected in their relative abilities to confer anchorage-independent growth. Our findings indicate that the effects of mutant PIK3CA are both cell type- and mutation-specific. Helical domain mutations in PIK3CA may confer a selective advantage in the urothelium in vivo by overcoming normal contact-mediated inhibitory signals and allowing proliferation in nutrient-limiting conditions. Mutant forms of PIK3CA may also stimulate intraepithelial cell movement, which could contribute to spread of cells within the urothelium.	bladder
miR-143, miR-222, and miR-452 are useful as tumor stratification and noninvasive diagnostic biomarkers for bladder cancer.	Altered microRNA (miRNA) expression may occur early in bladder cancer and may play a role in carcinogenesis and tumor behavior. We evaluated whether alterations in miRNA expression could improve disease stratification and outcome prognosis in bladder tumors and noninvasive diagnosis in urinary samples. miR-143, miR-222, and miR-452 expression levels were analyzed by quantitative RT-PCR (RT-qPCR) in paired urinary and matching tumors and in two independent prospective series of tumors and urinary specimens. Differential expression of miR-143, miR-222, and miR-452 in urine were verified by in situ hybridization in matching tumors. Tumor miRNA expression by RT-qPCR correlated with tumor grade, size, and presence of carcinoma in situ for miR-222, recurrence (miR-222 and miR-143), progression (miR-222 and miR-143), disease-specific survival (miR-222), and overall survival (miR-222). Protein expression patterns of potential miRNA targets, including vascular endothelial growth factor, BCL2, v-erb-b2 erythroblastic leukemia viral oncogene (ERBB) homolog 3, and ERBB4, were evaluated by IHC in tissue arrays containing tumors for which miRNAs were assessed by RT-qPCR. Target expression correlated with expression of their predicted regulatory miRNAs, recurrence (ERBB3), progression (ERBB4), disease-specific survival (ERBB3 and ERBB4), and overall survival (ERBB3 and ERBB4). Furthermore, RT-qPCR of miR-452 (area under the curve, 0.848) and miR-222 (area under the curve, 0.718) in urine provided high accuracies for bladder cancer diagnosis. Thus, bladder tumors were characterized by changes in miRNA expression that could aid in tumor stratification and clinical outcome prognosis, and miRNAs were detected in urinary specimens for noninvasive diagnosis.	bladder
Is bilateral extended pelvic lymphadenectomy necessary for strictly unilateral invasive bladder cancer?	PURPOSE: We determined the necessary extent of pelvic lymph node dissection in patients with strictly unilateral bladder cancer. MATERIALS AND METHODS: A total of 40 patients with cystectomy and unilateral bladder cancer preoperatively underwent flexible cystoscopy guided injection of radioactive technetium into the contralateral bladder wall. Preoperatively single photon emission computerized tomography was done in all cases to detect and localize radioactive lymph nodes. Radioactive lymph nodes were confirmed intraoperatively by a γ probe and removed separately. Backup extended pelvic lymph node dissection and ex vivo examination of the whole specimen with a γ camera were done to preclude missed radioactive lymph nodes. Single photon emission computerized tomography and intraoperative findings were used to generate a 3-dimensional projection model of each lymph node site. RESULTS: A total of 228 radioactive lymph nodes (median 6, range 1 to 17) were detected, including 193 (85%) on the ipsilateral side of injection and 35 (15%) on the contralateral side. Of the contralateral lymph nodes 6%, 5% and 4% were in the external iliac, obturator fossa and common iliac region, respectively, but none were in the contralateral internal iliac region. At least 1 radioactive lymph node per patient was detected on the ipsilateral side. Additional lymphatic drainage to the contralateral side was found in 40% of patients. CONCLUSIONS: Crossover lymphatic drainage is a common phenomenon and unilateral pelvic lymph node dissection would have missed radioactive lymph nodes in 40% of patients. However, we noted no lymphatic drainage to the contralateral internal iliac region. Thus, when bladder tumors are strictly unilateral, contralateral pelvic lymph node dissection can be limited to the obturator fossa, and the external and common iliac regions. Consequently preserving the contralateral autonomic nerves situated close to the internal iliac vessels does not compromise surgical radicality.	bladder
Half of visible and half of recurrent visible hematuria cases have underlying pathology: prospective large cohort study with long-term followup.	PURPOSE: Visible hematuria has a cancer yield of up to 24.2%. A large proportion of cases will have no etiology. In this study we determined the incidence of pathology (benign and malignant) in patients with visible hematuria and those with persistent and recurrent visible hematuria, and evaluated the policy for investigations. MATERIALS AND METHODS: Data were prospectively collected for 1,804 patients with visible hematuria at a United Kingdom teaching hospital from January 1999 to September 2007. In October 2010 the comprehensive hospital electronic database was checked for every individual patient to ensure no urological pathology was missed. All patients underwent standard hematuria investigations, including renal tract ultrasound and excretory urography or contrast enhanced computer tomography urogram, flexible cystoscopy and urine cytology. RESULTS: The male-to-female ratio was 4.8:1. Median age ± SD was 67 ± 17.0 years (range 21 to 109). Median followup was 6.6 ± 2.5 years (range 1.5 to 11.6). No urological pathology was found in 965 (53.5%) patients. Malignant urological disease was found in 386 (21.4%) patients, of whom 329 had bladder tumors. There were 32 patients with persistent visible hematuria and no malignancy. Repeat investigation was performed in 69 patients reporting recurrence. Of these patients 35 received a significant urological diagnosis, including 12 (17.4%) urological malignancies, while 34 (49.3%) still had no diagnosis. Limitations include the possibility of missing pathology. CONCLUSIONS: Almost 50% of patients presenting with visible hematuria will have a diagnosis. Therefore, all cases of visible hematuria require full standard investigations. Patients with no diagnosis can be discharged from followup. Recurrent visible hematuria after full initial negative findings requires repeat full standard investigations because 11.6% will have malignant pathology.	bladder
Exploring molecular genetics of bladder cancer: lessons learned from mouse models.	Urothelial cell carcinoma (UCC) of the bladder is one of the most common malignancies worldwide, causing considerable morbidity and mortality. It is unusual among the epithelial carcinomas because tumorigenesis can occur by two distinct pathways: low-grade, recurring papillary tumours usually contain oncogenic mutations in FGFR3 or HRAS, whereas high-grade, muscle-invasive tumours with metastatic potential generally have defects in the pathways controlled by the tumour suppressors p53 and retinoblastoma (RB). Over the past 20 years, a plethora of genetically engineered mouse (GEM) models of UCC have been developed, containing deletions or mutations of key tumour suppressor genes or oncogenes. In this review, we provide an up-to-date summary of these GEM models, analyse their flaws and weaknesses, discuss how they have advanced our understanding of UCC at the molecular level, and comment on their translational potential. We also highlight recent studies supporting a role for dysregulated Wnt signalling in UCC and the development of mouse models that recapitulate this dysregulation.	bladder
Bias in relative survival methods when using incorrect life-tables: lung and bladder cancer by smoking status and ethnicity in New Zealand.	Relative survival and excess mortality approaches are commonly used to estimate and compare net survival from cancer. These approaches are based on the assumption that the underlying (non-cancer) mortality rate of cancer patients is the same as that of the general population. This assumption is likely to be violated particularly in the context of smoking-related cancers. The magnitude of this bias has not been estimated. The objective of this article is to estimate the bias in relative survival ratios (RSRs) and excess mortality rate ratios (EMRRs) from using total population compared to correct subpopulation specific life-tables. Analyses were conducted on 1996-2001 linked census-cancer data (including smoking status) for people with lung and bladder cancer, using sex-specific (standard practice), sex- and ethnic-specific, sex- and smoking-specific and sex-, ethnic- and smoking-specific life-tables. Five-year RSRs using sex-specific life-tables, compared to fully stratified life-tables, were underestimated by 10-25% for current smoking and Maori populations. For example, the current smoker male bladder cancer RSR was 0.700 for sex-specific life-tables, compared to 0.838 for fully stratified life-tables. Similarly, EMRRs comparing current to never smokers and Maori to non-Maori were overestimated using sex-specific life-tables only: modestly only for lung cancer, but markedly for bladder cancer. For example, the EMRR comparing current to never smokers with bladder cancer in a fully adjusted regression model was 1.475 when using sex-specific life-tables only, but reduced to 1.098 when using fully stratified life-tables. Substantial bias can occur when estimating relative cancer survival across subpopulations if non-matching life-tables are used.	bladder
A case study of human papillomavirus-associated bladder carcinoma developing after urethral condyloma acuminatum.	We report a 35-year-old man with bladder carcinoma developing 2 months after urethral condyloma acuminatum, with an 8-year history of persistent human papilloma virus-58 infection in the urinary tract. DNA was extracted from paraffin-embedded tissue specimens. Human papilloma virus-6 and -58 were detected in the condyloma, whereas human papilloma virus-58 was detected in the carcinoma. In situ hybridization analysis also demonstrated high-risk human papilloma virus-DNA signals in the condyloma and carcinoma tissues. Immunohistochemistry showed that p16-INK4a and mcm-7, surrogate markers of oncogenic human papilloma virus E7 protein, were weakly expressed in the condyloma tissue but were strongly expressed in the carcinoma tissues, suggesting that human papilloma virus-58 was present in the episomal state in the condyloma, whereas human papilloma virus-58 DNA was integrated into the host cells and its infection may have a role in the development of bladder carcinoma. Human papilloma virus-58 was continuously detected in the urethral brushing samples 8 years after treatment for urethral condyloma, and human papilloma virus-58 infection was still persistent in the urethra.	bladder
Common genetic variants in the PSCA gene influence gene expression and bladder cancer risk.	Genome-wide association studies have identified a SNP, rs2294008, on 8q24.3 within the prostate stem cell antigen (PSCA) gene, as a risk factor for bladder cancer. To fine-map this region, we imputed 642 SNPs within 100 Kb of rs2294008 in addition to 33 markers genotyped in one of the reported genome-wide association study in 8,652 subjects. A multivariable logistic regression model adjusted for rs2294008 revealed a unique signal, rs2978974 (r(2) = 0.02, D' = 0.19 with rs2294008). In the combined analysis of 5,393 cases and 7,324 controls, we detected a per-allele odds ratio (OR) = 1.11 [95% confidence interval (CI) = 1.06-1.17, P = 5.8 × 10(-5)] for rs2294008 and OR = 1.07 (95% CI = 1.02-1.13, P = 9.7 × 10(-3)) for rs2978974. The effect was stronger in carriers of both risk variants (OR = 1.24, 95% CI = 1.08-1.41, P = 1.8 × 10(-3)) and there was a significant multiplicative interaction (P = 0.035) between these two SNPs, which requires replication in future studies. The T risk allele of rs2294008 was associated with increased PSCA mRNA expression in two sets of bladder tumor samples (n = 36, P = 0.0007 and n = 34, P = 0.0054) and in normal bladder samples (n = 35, P = 0.0155), but rs2978974 was not associated with PSCA expression. SNP rs2978974 is located 10 Kb upstream of rs2294008, within an alternative untranslated first exon of PSCA. The non-risk allele G of rs2978974 showed strong interaction with nuclear proteins from five cell lines tested, implying a regulatory function. In conclusion, a joint effect of two PSCA SNPs, rs2294008 and rs2978974, suggests that both variants may be important for bladder cancer susceptibility, possibly through different mechanisms that influence the control of mRNA expression and interaction with regulatory factors.	bladder
Role of diffusion-weighted magnetic resonance imaging in predicting sensitivity to chemoradiotherapy in muscle-invasive bladder cancer.	PURPOSE: In chemoradiation (CRT)-based bladder-sparing approaches for muscle invasive bladder cancer (MIBC), patients who respond favorably to induction CRT enjoy the benefits of bladder preservation, whereas nonresponders do not. Thus, accurate prediction of CRT sensitivity would optimize patient selection for bladder-sparing protocols. Diffusion-weighted MRI (DW-MRI) is a functional imaging technique that quantifies the diffusion of water molecules in a noninvasive manner. We investigated whether DW-MRI predicts CRT sensitivity of MIBC. METHODS AND MATERIALS: The study cohort consisted of 23 MIBC patients (cT2/T3 = 7/16) who underwent induction CRT consisting of radiotherapy to the small pelvis (40 Gy) with two cycles of cisplatin (20 mg/day for 5 days), followed by partial or radical cystectomy. All patients underwent DW-MRI before the initiation of treatment. Associations of apparent diffusion coefficient (ADC) values with CRT sensitivity were analyzed. The proliferative potential of MIBC was also assessed by analyzing the Ki-67 labeling index (LI) in pretherapeutic biopsy specimens. RESULTS: Thirteen patients (57%) achieved pathologic complete response (pCR) to CRT. These CRT-sensitive MIBCs showed significantly lower ADC values (median, 0.63 × 10(-3) mm(2)/s; range, 0.43-0.77) than CRT-resistant (no pCR) MIBCs (median, 0.84 × 10(-3) mm(2)/s; range, 0.69-1.09; p = 0.0003). Multivariate analysis identified ADC value as the only significant and independent predictor of CRT sensitivity (p < 0.0001; odds ratio per 0.001 ×10(-3) mm(2)/s increase, 1.03; 95% confidence interval, 1.01-1.08). With a cutoff ADC value at 0.74 × 10(-3) mm(2)/s, sensitivity/specificity/accuracy in predicting CRT sensitivity was 92/90/91%. Ki-67 LI was significantly higher in CRT-sensitive MIBCs (p = 0.0005) and significantly and inversely correlated with ADC values (ρ = -0.67, p = 0.0007). CONCLUSIONS: DW-MRI is a potential biomarker for predicting CRT sensitivity in MIBC. DW-MRI may be useful to optimize patient selection for CRT-based bladder-sparing approaches.	bladder
CT urography for hematuria.	Hematuria can signify serious disease such as bladder cancer, upper urinary tract urothelial cell carcinoma (UUT-UCC), renal cell cancer or urinary tract stones. CT urography is a rapidly evolving technique made possible by recent advances in CT technology. CT urography is defined as CT examination of the kidneys, ureters and bladder with at least one series of images acquired during the excretory phase after intravenous contrast administration. The reasoning for using CT urography to investigate hematuria is based on its high diagnostic accuracy for urothelial cell carcinoma (UCC) and favorable comparison with other imaging techniques. The optimum diagnostic imaging strategy for patients with hematuria at high-risk for UCC involves the use of CT urography as a replacement for other imaging tests (ultrasonography, intravenous urography, or retrograde ureteropyelography) and as a triage test for cystoscopy, resulting in earlier diagnosis and improved prognosis of bladder cancer, UUT-UCC, renal cell cancer and stones. Current problems with CT urography for investigating hematuria might be solved with a formative educational program simulating clinical reporting to reduce reader error, and a new technique for image-guided biopsy of UUT-UCC detected by CT urography for histopathological confirmation of diagnosis and elimination of false-positive results. CT urography is recommended as the initial imaging test for hematuria in patients at high-risk for UCC.	bladder
[Lymphadenectomy for bladder cancer: current status and controversies].	Pelvic lymph node dissection is an integral part of the radical cystectomy procedure for patients with muscle-invasive bladder cancer. The optimal extent of the lymphadenectomy (LND) and mainly the proximal template boundary remain controversial issues. In view of the existing mapping studies and retrospective analyses, extended LND up to the mid-upper third of the common iliac vessels appears to provide further prognostic and therapeutic benefit and therefore should be defined as standard LND. This applies for all procedures irrespective of the choice of surgical approach (open surgery, minimally invasive approach). In this context total lymph node count is not a quality criterion because nodal yield is overly influenced by the individual patient's anatomy, surgical technique, template applied and pathological work-up. Consecutively, considerable inter-institutional differences result, which render any comparison impossible. Lymph node density is thought to be a superior prognostic factor, but it is similarly influenced by the above-mentioned factors. Concerning molecular techniques to improve the sensitivity of postoperative nodal staging further research is necessary. The two ongoing prospective randomized trials will potentially help to further define the optimal LND template.	bladder